May 21, 2008This article helps us understand what is causing dementia, Alzheimer’s, Parkinson’s, Huntington’s, autism, ADD, ADHD, and other neurodegenerative challenges. These devastating diseases are caused by misfolded (mutated) toxic proteins. An article was released today by ScienceDaily on the story we reported recently about what scientists are now saying causes neurodegenerative diseases. Connect the dots and they lead to sugars, specifically trehalose for helping correct the gene expression caused by the toxicity in the RNA. Bottom line: Get the toxin out.

Lowering the cost of healthcare starts with cutting off the supply line of toxins coming into the body. The second and third steps are to get the toxins out of the system and get good nutrients into the body.

How RNA Toxicity Contributes To Neurodegenerative Disease.

ScienceDaily (May 21, 2008) — Expanding on prior research performed at the University of Pennsylvania, Penn biologists have determined that faulty RNA, the blueprint that creates mutated, toxic proteins, contributes to a family of neurodegenerative disorders in humans.

Nancy Bonini, professor in the Department of Biology at Penn and an investigator of the Howard Hughes Medical Institute, and her team previously showed that the gene that codes for the ataxin-3 protein, responsible for the inherited neurodegenerative disorder Spinocerebellar ataxia type 3, or SCA3, can cause the disease in the model organism Drosophila. SCA3 is one of a class of human diseases known as polyglutamine repeat diseases, which includes Huntington's disease. Previous studies had suggested that the disease is caused largely by the toxic polyglutamine protein encoded by the gene.

The current study, which appears in the journal Nature, demonstrates that faulty RNA, the blueprint for the toxic polyglutamine protein, also assists in the onset and progression of disease in fruit fly models.

“The challenge for many researchers is coupling the power of a simple genetic model, in this case the fruit fly, to the enormous problem of human neurodegenerative disease,” Bonini said. “By recreating in the fly various human diseases, we have found that, while the mutated protein is a toxic entity, toxicity is also going on at the RNA level to contribute to the disease.”

To identify potential contributors to ataxin-3 pathogenesis, Bonini and her team performed a genetic screen with the fruit fly model of ataxin-3 to find genes that could change the toxicity. The study produced one new gene that dramatically enhanced neurodegeneration. Molecular analysis showed that the gene affected was muscleblind, a gene previously implicated as a modifier of toxicity in a different class of human disease due to a toxic RNA. These results suggested the possibility that RNA toxicity may also occur in the polyglutamine disease situation.

The findings indicated that an RNA containing a long CAG repeat, which encodes the polyglutamine stretch in the toxic polyglutamine protein, may contribute to neurodegeneration beyond being the blueprint for that protein. This raised the possibility that expression of the RNA alone may be damaging.

Long CAG repeat sequences can bind together to form hairpins, dangerous molecular shapes. The researchers therefore tested the role of the RNA by altering the CAG repeat sequence to be an interrupted CAACAG repeat that could no longer form a hairpin. Such an RNA strand, however, would still be a blueprint for an identical protein. The researchers found that this altered gene caused dramatically reduced neurodegeneration, indicating that altering the RNA structure mitigated toxicity.

To further implicate the RNA in the disease progression, the researchers then expressed just a toxic RNA alone, one that was unable to code for a protein at all. This also caused neuronal degeneration. These findings revealed a toxic role for the RNA in polyglutamine disease, highlighting common components between different types of human triplet repeat expansion diseases. Such diseases include not only the polyglutamine diseases but also diseases like myotonic dystrophy and fragile X.

The family of diseases called polyglutamine repeat disorders arise when the genetic code of a CAG repeat for the amino acid glutamine stutters like a broken record within the gene, becoming very long. This leads to an RNA — the blueprint for the protein — with a similar long run of CAG. During protein synthesis, the long run of CAG repeats are translated into a long uninterrupted run of glutamine residues, forming what is known as a polyglutamine tract. The expanded polyglutamine tract causes the errant protein to fold improperly, leading to a glut of misfolded protein collecting in cells of the nervous system, much like what occurs in Alzheimer's and Parkinson's diseases.

Polyglutamine disorders are genetically inherited ataxias, neurodegenerative disorders marked by a gradual decay of muscle coordination, typically appearing in adulthood. They are progressive diseases, with a correlation between the number of CAG repeats within the gene, the severity of disease and age at onset.

In addition to Bonini, researchers whose work contributed to this study are Ling-Bo Li, formerly in the Department of Biology at Penn and now with the Department of Biochemistry at the University of Utah, and Zhenming Yu and Xiuyin Teng of the Department of Biology at Penn and the Howard Hughes Medical Institute.

Funding for this study was provided by the National Institute of Neurological Disorders and Stroke.

hlc

J.C. Spencer's book is a lot less expensive than that one. "Expand Your Mind - Improve Your Brain" is the first major book to have on one's shelf about HD. I got mine by downloading the entire book. I have bound the entire 500 pages into a nice book. I will take a look at the one at Targets.

« Last Edit: May 19, 2008, 01:08:57 PM by JC Spencer »

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kendersa

Books like this give me great hope and continued faith that the cure is out there for HD. This will be yet another book that I will read and hope to understand. I have found it at target for $124 if anyone is interested.

A News Report out of Dublin, Ireland this morning supports our own findings about glycomics and cell damage repair and neural degeneration and repair. A new book is touted as the first book linking glycomics and nerve cell damage repair. The title of the book is "Neural Degeneration and Repair: Gene Expression Profiling, Proteomics and Systems Biology". The book is selling for $113 EU which is about $175 US. Well, it is not quite the first book to link glycomics to neurodegenerative repair. Read more about Expand Your Mind - Improve Your Brain by clicking on the cover of my book from the Home Page of www.endowmentmed.org

May 12, 2008 11:00 PM Eastern Daylight Time

Analysis of Nerve Cell Damage and Repair using Genomics, Transcriptomics, Proteomics, Glycomics and Systems Biology DUBLIN, Ireland--(BUSINESS WIRE)--Research and Markets (http://www.researchandmarkets.com/reports/c91485) has announced the addition of "Neural Degeneration and Repair: Gene Expression Profiling, Proteomics and Systems Biology" to their offering.

With contributions from leading scientists around the world, this is the first book focussing on the analysis of nerve cell damage and repair using genomics, transcriptomics, proteomics, glycomics and systems biology in order to develop novel therapeutic and diagnostic approaches for neural diseases.

Following an introduction into the microarray technology in translational neuroscience, the book goes on to look at the use of '-omics' technologies to analyse molecular changes in traumatic injury, neuron degeneration and regeneration, oxidative stress response, neuropathic pain manifestation, and more. The work covers central nervous system as well as peripheral nervous system pathologies. This novel approach makes the book an indispensable companion for neurobiologists, neurologists, cell and molecular biologists, geneticists, and analytical chemists.

The Author is Hans Werner Müller who has been Professor of Molecular Neurobiology at Düsseldorf University since 1993. From 2001 onwards he has acted as the founder of the Neuraxo Biotec GmbH company, where he is also Chairman of the board of directors. He has published more than 150 scientific articles in the field of neurobiology and neuroscience and is an active member of many scientific societies including the American Society for Neurosciences, and the German Society for Neuroscience, where he is chairman of the molecular neurobiology section.